Prognostic analysis of esophageal carcinoma patients with stump carcinoma and atypical hyperplasia after esophagectomy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the prognostic factors for esophageal carcinoma patients with stump carcinoma and atypical hyperplasia after esophagectomy.</p><p><b>METHODS</b>From August 2006 to December 2010, 182 esophageal carcinoma patients with stump carcinoma and atypical hyperplasia after esophagectomy treated in our hospital were involved in this study, including 60 cases with grade I-II atypical hyperplasia, 23 cases with grade III atypical hyperplasia, 37 cases with carcinoma in situ, and 62 cases with invasive carcinoma. Prognostic factors for these patients were analyzed.</p><p><b>RESULTS</b>The 1-, 2-, 3- and 4-year locoregional control rates of these 182 patients were 77.1%, 63.3%, 60.3% and 60.3%, respectively, and the over-all cumulative survival rates were 78.6%, 63.9%, 46.3% and 41.0%, respectively. A total of 56 cases suffered from locoregional recurrence (56/182, 30.8%), including anastomotic recurrence and lymph node metastasis. The number of locoregional recurrence patients of grade I-II of atypical hyperplasia was 13(13/60, 21.7%), grade III atypical hyperplasia and carcinoma in situ 21 (21/60, 35.0%), and invasive carcinoma 22 (22/62, 35.5%). There were no significant differences among the three groups(χ(2) = 3.485, P = 0.175). There were significant differences in locoregional control rate and survival rate among the four treatment groups (P < 0.05). For patients with stump grade I∼II atypical hyperplasia and different stage positive stump margin, the 1-, 2-, 3- and 4-year survival rates of the four treatment groups had significant differences (P < 0.05). As for locoregional control rates, there were no significant differences in the four groups (P > 0.05). Univariate analysis showed that tumor length, depth of invasion, number of metastatic lymph nodes, number of lymph node metastatic fields, pTNM stage, stump pathological grade and treatment modality were main influencing factors for survival rate (P < 0.05);invasion depth, stump pathological grade and treatment modality were important factors for locoregional control. Multivariate Cox regression analysis showed that tumor length, number of metastatic lymph nodes, stump pathological grade and treatment modality were independent influencing factors for survival (all P < 0.05);invasion depth, stump pathological grade and treatment modality were independent influencing factors for locoregional control (all P < 0.05).</p><p><b>CONCLUSIONS</b>For the patients with stump carcinoma and atypical hyperplasia after esophagectomy, tumor length, number of metastatic lymph nodes, stump pathological grade and treatment modality are independent influencing factors for long-term survival, and invasion depth, stump pathological grade and treatment modality are independent influencing factors for locoregional control.</p>

Bidirectional effect of MnSOD overexpression on the proliferation of esophageal cancer cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To construct a recombinant lentiviral vector for manganese superoxide dismutase (MnSOD) gene expression, and observe its effect on the proliferation of esophageal cancer cells in vitro.</p><p><b>METHODS</b>Chemical methods were employed for synthesis of the MnSOD cDNA sequence sections, along with the attB sites. Target gene fragment was constructed on the pMD-18T vector, and the recombinant plasmid pDONR221 was obtained after BP recombination reaction. Sequencing was followed by LR recombination reaction between the plasmid and DEST to obtain the lentiviral vector, which worked with helper plasmid for co-transfection of human embryonic kidney epithelial cells (293T cells). Amplification was done to determine its titer, and both transfection and selection procedures were made to get two stable transfected esophageal cancer TE-1 cell lines with medium MnSOD expression (TE-1Mm cells) and high MnSOD expression (TE-1Mh cell), and empty vector cell (TE-1Mn cells). Reverse transcription polymerase chine reaction (RT-PCR), immunofluorescence, immunocytochemistry and Western blot were used to detect the target gene with respect to its expression in the TE-1 cells. Additionally, colorimetric 3-[4,5-dimethy thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, agar colony formation assay, annexin V-FITC/PI staining and flow cytometry experiments were also conducted as to observe the influence of the medium and high MnSOD overexpressions on the proliferation of esophageal cancer cells.</p><p><b>RESULTS</b>RT-PCR indicated that the transfected TE-1 cells showed positive MnSOD expression at different levels. Immunofluorescence, immunocytochemistry and Western blot suggested that TE-1Mm cells and TE-1Mh cells had MnSOD protein expression at different levels. MTT assay indicated that TE-1Mm cells had a significantly decreased survival rate compared with that of the two control cells (TE-1 cells and TE-1Mn cells), and TE-1 Mh cells had an significantly increased survival rate (P<0.05). The colony formation ability of TE-1Mm cells was (23.0 +/- 2.7)%, and that of TE-1Mh cells was (45.3 +/- 4.5)%, significantly different form the (34.7 +/- 4.2)% in TE-1 cells and (33.7 +/- 4.7)% in TE-1Mn cells (P<0.05). Annexin V-FITC/PI double staining experiment of the stably transfected cells cultured for 48 h showed that the early apoptosis rate in TE-1Mm cells was (10.6 +/- 1.0)%, significantly higher than (2.6 +/- 0.2)% in the TE-1 cells, (2.5 +/- 0.6)% in the empty vector cells and (1.0 +/- 0.1)% in the TE-1Mh cels (P<0.05). The fluorescence index (FI) of mitochondrial apoptosis of TE-1Mm cells was 0.948 +/- 0.019, significantly lower than that of TE-1 cell (1.000 +/- 0.022) and empty vector The fluorescence index of TE-1Mn cells (0.997 +/- 0.023) and TE-1 cells (1.000 +/- 0.022) were significant different from that of 0.948 +/- 0.019 in TE-1Mm cells and 1.076 +/- 0.022 in TE-1Mh cells, indicating a significant difference of mitochondrial apoptosis between the cell groups. FCM results indicated that the ROS fluorescence index of TE-1Mm cells was 0.859 +/- 0.040, that of TE-1Mh cells was 0.763 +/- 0.039, significantly lower than that of TE-1 cells (1.000 +/- 0. 042) and empty vector cells (1.002 +/- 0.047) (P<0.05).</p><p><b>CONCLUSIONS</b>Stably transfected cell lines with MnSOD expression have been successfully established. MnSOD overexpression shows bidirectional effect on the proliferation of esophageal cancer cells.</p>

Expression of MnSOD mRNA and protein in esophageal squamous cell carcinoma and its clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of manganese superoxide dismutase (MnSOD) and to determine the relationship between MnSOD expression and clinicopathological features, biological behaviors in esophageal carcinoma.</p><p><b>METHODS</b>Immunohistochemistry (SP) and RT-PCR were respectively used to detect the expression of MnSOD in 45 specimens of esophageal carcinoma tissues and normal esophageal mucosa (5 cm distant from the margin of cancer).</p><p><b>RESULTS</b>The positive rate of MnSOD protein expression was 31.1% in esophageal carcinoma tissues, significantly lower than 86.7% in the normal tissues (P < 0.05). The expressions of MnSOD mRNA and protein were significantly correlated with the lesion length, depths of invasion and histological grade (P < 0.05), but not with lymph node metastasis, lesion site and gross type of the tumor (P > 0.05). The relative content of MnSOD mRNA was (0.310 ± 0.036) and (0.482 ± 0.053) in the cancer and normal tissues, respectively, with a significant difference between the two groups (P < 0.05). The relative content of MnSOD mRNA was significantly related to lesion length, depths of invasion and histological grade (P < 0.05), but not correlated with lymph node status, lesion site and gross type of the tumor (P > 0.05).</p><p><b>CONCLUSION</b>The expression of MnSOD protein and mRNA is decreased in esophageal carcinoma, suggesting that MnSOD gene may be closely associated with the carcinogenesis and the degree of malignancy. Detection of MnSOD expression may be useful in diagnosis, treatment and prognosis of esophageal carcinoma.</p>

Expression of E-cadherin in nasopharyngeal carcinoma and its relationship with cervical lymph node metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of E-cadherin in nasopharyngeal carcinoma (NPC) and its relationship with cervical lymph node metastasis.</p><p><b>METHODS</b>The expression of E-cadherin in 80 patients with NPC was detected by immunohistochemistry.</p><p><b>RESULTS</b>Lower expression of E-cadherin was associated with advanced N-stage of the tumor (P = 0.018). There was no significant correlation between the expression of E-cadherin and lymph node size (P = 0.435). The expression of E-cadherin was higher in patients with cervical lymph node metastasis limited to a single area than that distributing in some scattered areas (P = 0.000). There was a trend that the expression of E-cadherin in the cases with the tumor and lymph nodes in the same side was higher (56.5%) than that in the patients with bilateral lymph node metastases (32.6%), however, the difference was not significant (P = 0.059). The expression rates of E-cadherin in patients with lymph node metastasis in levels II, III and Va were higher than that in levels I, IV, Vb and VI, but with a non-significant difference (P = 0.059).</p><p><b>CONCLUSION</b>The expression of E-cadherin has influence on the lymph node metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively correlated with the numbers of the lymph node metastases and the metastasis distance, i.e. a lower expression of E-cadherin leads to an advanced N-stage. The lymph node metastasis of nasopharyngeal cancer from above to below is more considerably influenced by E-cadherin expression than the metastasis towards contralateral lymph nodes.</p>

Association of single nucleotide polymorphism of MnSOD gene with carcinogenesis and development of esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association of single nucleotide polymorphism (SNP) of manganese superoxide dismutase (MnSOD) gene with carcinogenesis and progression of esophageal squamous cell carcinoma.</p><p><b>METHODS</b>The MnSOD9 T-->C SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 103 patients with esophageal squamous cell carcinoma and 195 healthy controls.</p><p><b>RESULTS</b>A significant difference was observed in the MnSOD allelotype distribution among esophageal squamous cell carcinomas and healthy controls (chi(2) = 4.645, P < 0.05). Individuals with the 9 C allele had a significantly higher risk to develop esophageal squamous cell carcinoma compared with those with the TT allele. The frequency of C allelotype among patients with lesions of different lengths (</= 5 cm and > 5 cm) was 16.3% and 36.7%, respectively. A significant difference was observed in the MnSOD allelotype distribution between patients with lesions of different lengths (chi(2) = 5.147, P < 0.05). No significant association of the MnSOD polymorphism at 9 T-->C with the tumor site, maximal length and clinical staging was found in esophageal squamous cell carcinoma.</p><p><b>CONCLUSION</b>Single nucleotide polymorphism (SNP) of MnSOD gene may be correlated with the susceptibility and disease progression of esophageal squamous cell carcinoma, and may become a tumor marker for prediction of this cancer.</p>